phase 1 study of f182112 in patients with relapsed or refractory multiple myeloma

Conditions: Dose-Escalation Study, Relapsed or Refractory Multiple Myeloma

Summary: this trial is a multiple center, open-label, dose escalation phase ⅰ clinical study. the purpose is to evaluate the safety and tolerability of f182112 when infused intravenously (iv) and determine the maximum tolerated dose (mtd) and/or the recommended phase 2 dose (rp2d) of f182112 when infused iv.

to assess the safety, tolerability, and dose-limiting toxicities (dlts) and to determine a recommended phase 2 dose regimen (rp2dr) of f182112 as monotherapy in patients with relapsed or refractory multiple myeloma (mm).

Eligibility criteria:
inclusion criteria: * 1) willing and able to provide signed and dated informed consent prior to any study-related procedures and willing and able to comply with all study procedures; 2) male or female ≥ 18 years; 3) patient has a history of multiple myeloma with relapsed and refractory disease, and must: 1. relapsed after an autologous stem cell transplant (asct), or not suitable for asct; 2. must have received at least 2 prior multiple myeloma treatment regimens (not including autologous stem cell transplant) including a proteasome inhibitor, an immunomodulatory agent; 4) ecog of 0-2; 5) patients must have measurable disease, including at least one of the criteria below: 1. m-protein ≥ 0.5 g/dl by spep/immunofixation or 2. ≥ 200 mg/24 hours urine collection by upep or 3. serum free light chain (flc) levels \> 100 mg/l (milligrams/liter involved light chain) and an abnormal kappa/lambda (κ/λ) ratio in patients without detectable serum or urine m-protein; 6) adequate hepatic function as evidenced by meeting all the following requirements: 1. blood routine: absolute neutrophil count (anc) ≥ 1.0×109/l, hemoglobin (hb) ≥70g/l, platelet ≥ 50×109/l; 2. liver function: total bilirubin ≤ 1.5 × upper limit of normal (uln), alanine aminotransferase (alt) ≤ 2.5 × uln, aspartate aminotransferase (ast) ≤ 2.5 × uln; 3. renal function: calculated creatinine clearance (crcl) ≥ 30 ml/min (cockroft-gault equation). 7) recovery to grade 0-1 from adverse events related to prior anticancer therapy except alopecia, ≤ grade 2 sensory neuropathy, lymphopenia, and endocrinopathies controlled with hormone replacement therapy. exclusion criteria: * 1) patient has primary light chain amyloidosis or plasma cell leukemia; 2) patient has symptomatic central nervous system involvement of multiple myeloma; 3) received systemic anti-myeloma therapy within 2 weeks, or received plasma exchange within 4 weeks; 4) received any experimental drugs within 4 weeks or 5 half-lives (whichever is shorter); 5) patient has received ≥ 40 mg/day dexamethasone equivalent within 7 days before starting f182112. short term use of corticosteroids at doses equivalent to \> 10 mg/d of prednisone； 6) received any monoclonal antibody therapy within 30 days; 7) prior treatment with any b cell maturation antigen (bcma) targeted therapy; 8) patient had a prior allogeneic stem cell transplant or had a prior autologous stem cell transplant ≤ 3 months prior to starting f182112; 9) live virus vaccine within 30 days prior to study entry; 10) major surgery within 4 weeks prior to study entry; 11) concurrent malignancy within 3 years prior to entry other than adequately treated cervical carcinoma-in-situ, localized squamous cell cancer of the skin, basal cell carcinoma, prostate cancer under active surveillance, prostate cancer that has undergone definitive treatment, ductal carcinoma in situ of the breast, or ≤ t1 urothelial carcinoma; 12) patients with active mucosa or visceral bleeding; 13) severe cardiovascular disease, including cva, tia, myocardial infarction, or unstable angina within 6 months of study entry; nyha class iii or iv heart failure within 6 months of study entry; uncontrolled arrhythmia within 6 months of study entry. patients with a rate-controlled arrhythmia may be eligible for study entry at the discretion of the medical monitor; 14) active infection requiring antibiotic, antiviral or antifungul therapy; 15) active viral hepatitis; 16) has a history of immunodeficiency, include hiv infection; 17) treponema pallidum infection; 18) received any experimental drugs or anti-tumor drugs within 2 weeks; 19) subject has any condition that confounds the ability to interpret data from the study; 20) females and males must practice true abstinence or agree to contraceptive methods throughout the study, and 6 months after the last giving f182112; 21) any condition that the investigator or primary physician believes may not be appropriate for participating the study.